Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: data from the HIGHCARE project

被引：120

作者：

Piperno, Alberto ^{[1
,2
,3
]}

Galimberti, Stefania ^{[4
]}

Mariani, Raffaella ^{[1
,2
]}

Pelucchi, Sara ^{[1
,2
]}

Ravasi, Giulia ^{[1
,2
]}

Lombardi, Carolina ^{[5
]}

Bilo, Grzegorz ^{[5
]}

Revera, Miriam ^{[5
]}

Giuliano, Andrea ^{[1
,2
,5
]}

Faini, Andrea ^{[5
]}

Mainini, Veronica ^{[6
]}

Westerman, Mark ^{[7
]}

Ganz, Tomas ^{[8
]}

Valsecchi, Maria Grazia ^{[4
]}

Mancia, Giuseppe ^{[1
,2
]}

Parati, Gianfranco ^{[1
,2
,5
]}

机构：

[1] Univ Milano Bicocca, San Gerardo Hosp, I-20052 Monza, Italy

[2] Univ Milano Bicocca, Dept Clin Med & Prevent, I-20052 Monza, Italy

[3] Consortium Human Mol Genet, Monza, Italy

[4] Univ Milano Bicocca, Dept Clin Med & Prevent, Ctr Biostat Clin Epidemiol, I-20052 Monza, Italy

[5] Ist Auxol Italiano, Dept Cardiol, Milan, Italy

[6] Univ Milano Bicocca, Dept Expt Med, I-20052 Monza, Italy

[7] Intrins LifeSci LLC, La Jolla, CA USA

[8] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Med, Los Angeles, CA 90095 USA

来源：

BLOOD | 2011年 / 117卷 / 10期

关键词：

IRON-METABOLISM; EXPRESSION; ANEMIA; GENE; DIFFERENTIATION; PROTEINS; ALTITUDE; GDF15;

D O I：

10.1182/blood-2010-08-299859

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Iron is tightly connected to oxygen homeostasis and erythropoiesis. Our aim was to better understand how hypoxia regulates iron acquisition for erythropoiesis in humans, a topic relevant to common hypoxia-related disorders. Forty-seven healthy volunteers participated in the HIGHCARE project. Blood samples were collected at sea level and after acute and chronic exposure to high altitude (3400-5400 m above sea level). We investigated the modifications in hematocrit, serum iron indices, erythropoietin, markers of erythropoietic activity, interleukin-6, and serum hepcidin. Hepcidin decreased within 40 hours after acute hypoxia exposure (P < .05) at 3400 m, reaching the lowest level at 5400 m (80% reduction). Erythropoietin significantly increased (P < .001) within 16 hours after hypoxia exposure followed by a marked erythropoietic response supported by the increased iron supply. Growth differentiation factor-15 progressively increased during the study period. Serum ferritin showed a very rapid decrease, suggesting the existence of hypoxia-dependent mechanism(s) regulating storage iron mobilization. The strong correlation between serum ferritin and hepcidin at each point during the study indicates that iron itself or the kinetics of iron use in response to hypoxia may signal hepcidin down-regulation. The combined and significant changes in other variables probably contribute to the suppression of hepcidin in this setting. (Blood. 2011;117(10):2953-2959)

引用

页码：2953 / 2959

页数：7

共 38 条

[1]

[Anonymous], 2004, Applied Longitudinal Analysis

[2] Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin [J].